The Nyainqêntanglha polymetallic belt (NPB) is western China's foremost skarn Pb–Zn metallogenic belt. Significant progress has been made in determining these ore deposits' age and origin. However, the precipitation mechanisms and mineralization controls for these deposits remain unresolved. 40Ar/39Ar dating, fluid inclusion (FI), and H-O-S-Pb isotopic data are presented for the Nuocang deposit, a newly discovered polymetallic Pb-Zn skarn deposit in the western NPB, with the goal to trace age and, especially, the major fluid processes associated with hydrothermal evolution leading to the precipitation of ore. The muscovite yields an 40Ar-39Ar plateau age of 59.68 ± 0.60 Ma, which closely resembles typical skarn deposits within the NPB, indicating that it formed during the main collisional stage of the India–Eurasia continent. In the Nuocang base-metal skarn deposit, three ore-related stages can be discerned and subdivided: 1) the pre-ore stage, containing the prograde and early retrograde metasomatic skarn minerals, 2) the syn-ore stage, including the late retrograde metasomatic minerals and sulfides, and 3) the post-ore stage of quartz, calcite, and chlorite alteration. Correspondingly, three types of FI (L, V, and S type) have been identified. The ore-forming fluids evolved from moderate to high temperature between 340 and 440 °C primarily, but up to 571 °C, and moderate to high salinity (concentrated ∼8–18 wt% NaCl-equiv., but up to 48.1 wt% NaCl equiv.) in the pre-ore stage. During the syn-ore stage, the fluids were at low to moderate temperature (between 200 and 320 °C) and low salinity (∼2 to 12 wt% NaCl-equiv.) and developed in low temperature (∼120–200 °C) and low salinity (∼2–8 wt% NaCl equiv.) in the post-ore stage. The calculated δDH2O values of the transparent minerals were −180 to −106 ‰ during the pre-ore stage, −141 to −59 ‰ during the syn-ore stage, and −152 to −105 ‰ during the post-ore stage. The δ18OH2O values were −1.2 to 3.8 ‰ during the pre-ore stage, −4.7 to −2.3 ‰ during the syn-ore stage, and −10.9 to −5.0 ‰ during the post-ore stage, respectively.Based on these results, the magmatic fluids appeared to have gradually evolved into meteoric. Meteoric water is believed to play a significant role in metal deposition within magmatic-hydrothermal systems. Locally, boiling is also considered another key mechanism for ore precipitation. The S-Pb isotope values of the sulfide metals indicate that the metallogenic materials were predominantly derived from an upper crustal source mixing with minor amounts of mantle–derived components. This study suggests that the fluid mixing is related to geostatic pressure variations and infiltration of meteoric waters into the hydrothermal system and are key mechanisms triggering Pb-Zn ore deposition in the NPB.